title: Microscopic imaging mass spectrometry assisted by on-tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts.
abstract: Imaging MS combined with CE/MS serves as a method to provide semi-quantitative and spatial information of small molecular metabolites in tissue slices. However, not all metabolites including amino acids have fully been visualized, because of low-ionization efficiency in MALDI MS. This study aimed to acquire semi-quantitative spatial information for multiple amino acids in frozen tissue slices. As a derivatization reagent, p-N,N,N-trimethylammonioanilyl N'-hydroxysuccinimidyl carbamate iodide (TAHS) was applied to increase their ionization efficiency and detection sensitivity. Semi-quantitative MALDI-imaging MS allowed us to visualize and quantify free amino acid pools in human colon cancer xenografts using a model of liver metastases in super-immunodeficient NOD/scid/γ(null) mice (NOG mice). Because the m/z values of several TAHS-derivatized amino acids overlap with those of the 2,5-dihydroxybenzoic acid background and other endogenous compounds, we imaged them with tandem MS. The results indicated that regional contents of glutamate, glutamine, glycine, leucine/isoleucine/hydroxyproline, phenylalanine, and alanine were significantly elevated in metastatic tumors versus parenchyma of tumor-bearing livers. On-tissue TAHS derivatization thus serves as a useful method to detect alterations in many amino acid levels in vivo, thereby enabling understanding of the spatial alterations of these metabolites under varied disease conditions including cancer.
authors.affiliation: Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan; Institute for Innovation, Ajinomoto Co., Inc, Kawasaki, Kanagawa, Japan.
authors.forename: Sakino
authors.initials: S
authors.lastname: Toue
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugiura
authors.forename: Akiko
authors.initials: A
authors.lastname: Kubo
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Ohmura
authors.forename: Sachise
authors.initials: S
authors.lastname: Karakawa
authors.forename: Toshimi
authors.initials: T
authors.lastname: Mizukoshi
authors.forename: Junya
authors.initials: J
authors.lastname: Yoneda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyano
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Noguchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Kabe
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
mesh_terms: D000596:Amino Acids / Q000302:isolation & purification* / Q000378:metabolism; D000818:Animals; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D009362:Neoplasm Metastasis; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000596:Amino Acids
keywords: Amino acid; Cancer metastasis; Imaging MS; Metabolism; On-tissuederivatization; Technology